Drug–drug interactions involving classic psychedelics: A systematic review
Andreas Halman, Geraldine Kong, Jerome Sarris, Daniel Perkins
Journal of Psychopharmacology November 20, 2023 DOI: 10.1177/02698811231211219 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Topics | LSD Mescaline Psilocybin |
| Keywords | Hallucinogen Psycinfo Pharmacology Recreational drug Mood Psychotropic drug Dissociative Medline |
| Citations | 42 |
| Key findings | Combining classic psychedelics with other drugs can attenuate, potentiate, or leave unchanged their effects, with no serious adverse events reported beyond a few case studies. |
Abstract
Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are potent psychoactive substances that have been studied for their physiological and psychological effects. However, our understanding of the potential interactions and outcomes when using these substances in combination with other drugs is limited. This systematic review aims to provide a comprehensive overview of the current research on drug–drug interactions between classic psychedelics and other drugs in humans. We conducted a thorough literature search using multiple databases, including PubMed, PsycINFO, Web of Science and other sources to supplement our search for relevant studies. A total of 7102 records were screened, and studies involving human data describing potential interactions (as well as the lack thereof) between classic psychedelics and other drugs were included. In total, we identified 52 studies from 36 reports published before September 2, 2023, encompassing 32 studies on LSD, 10 on psilocybin, 4 on mescaline, 3 on DMT, 2 on 5-MeO-DMT and 1 on ayahuasca. These studies provide insights into the interactions between classic psychedelics and a range of drugs, including antidepressants, antipsychotics, anxiolytics, mood stabilisers, recreational drugs and others. The findings revealed various effects when psychedelics were combined with other drugs, including both attenuated and potentiated effects, as well as instances where no changes were observed. Except for a few case reports, no serious adverse drug events were described in the included studies. An in-depth discussion of the results is presented, along with an exploration of the potential molecular pathways that underlie the observed effects.
Comparable studies
Other systematic reviews and meta-analyses on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids Humans (ritual ayahuasca use) | 2006 | Systematic review | |
| Psychedelic‐assisted treatment for substance use disorder: A narrative systematic review Participants in studies of psychedelic-assisted treatment for alcohol, tobacco, and... | 2025 | Systematic review | n = 2,035 |
| The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies Preclinical animal and in vitro studies | 2024 | Systematic review | |
| Drug-drug interactions between classic psychedelics and psychoactive drugs: a systematic review Humans | 2023 | Systematic review | |
| A Systematic Review of the Neurocognitive Effects of Psychedelics in Healthy Populations: Implications for Depressive Disorders and Post-Traumatic Stress Disorder Healthy individuals and patients with PTSD or MDD | 2024 | Systematic review | n = 43 |
Citations in the library
Cited by 42
- Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response Journal of Psychopharmacology September 20, 2024
- Psilocybin: From Psychiatric Pariah to Perceived Panacea American Journal of Psychiatry 2025
- Harnessing Pharmacogenomics in Clinical Research on Psychedelic‐Assisted Therapy Clinical Pharmacology & Therapeutics September 30, 2024
- Why N,N-dimethyltryptamine matters: unique features and therapeutic potential beyond classical psychedelics. Frontiers in Psychiatry November 6, 2024
- Review of Psilocybin Use for Depression among Cancer Patients after Approval in Oregon Cancers April 27, 2024
and 37 more in the library
Cites 56
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Elife October 25, 2018
- Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca Journal of Ethnopharmacology April 1, 1984
- Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids Pharmacognosy Reviews/Bioinformatics Trends/Pharmacognosy review 2013
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
and 51 more in the library